Fischmann T O, Hruza A, Niu X D, Fossetta J D, Lunn C A, Dolphin E, Prongay A J, Reichert P, Lundell D J, Narula S K, Weber P C
Structural Chemistry Department, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Nat Struct Biol. 1999 Mar;6(3):233-42. doi: 10.1038/6675.
Crystal structures of human endothelial nitric oxide synthase (eNOS) and human inducible NOS (iNOS) catalytic domains were solved in complex with the arginine substrate and an inhibitor S-ethylisothiourea (SEITU), respectively. The small molecules bind in a narrow cleft within the larger active-site cavity containing heme and tetrahydrobiopterin. Both are hydrogen-bonded to a conserved glutamate (eNOS E361, iNOS E377). The active-site residues of iNOS and eNOS are nearly identical. Nevertheless, structural comparisons provide a basis for design of isozyme-selective inhibitors. The high-resolution, refined structures of eNOS (2.4 A resolution) and iNOS (2.25 A resolution) reveal an unexpected structural zinc situated at the intermolecular interface and coordinated by four cysteines, two from each monomer.
人内皮型一氧化氮合酶（eNOS）和人诱导型一氧化氮合酶（iNOS）催化结构域的晶体结构分别通过与精氨酸底物和抑制剂S-乙基异硫脲（SEITU）形成复合物而得到解析。小分子结合在含有血红素和四氢生物蝶呤的较大活性位点腔内的一个狭窄裂隙中。两者都通过氢键与一个保守的谷氨酸（eNOS的E361、iNOS的E377）相连。iNOS和eNOS的活性位点残基几乎相同。然而，结构比较为同工酶选择性抑制剂的设计提供了基础。eNOS（分辨率为2.4 Å）和iNOS（分辨率为2.25 Å）的高分辨率精制结构揭示了一个位于分子间界面且由四个半胱氨酸配位的意外结构锌，每个单体各提供两个半胱氨酸。
